Exploring neuroadaptive cellular pathways in chronic morphine exposure: An in-vitro analysis of cabergoline and Mdivi-1 co-treatment effects on the autophagy-apoptosis axis.

The complex impacts of prolonged morphine exposure continue to be a significant focus in the expanding area of addiction studies. This research investigates the effectiveness of a combined treatment using Cabergoline and Mdivi-1 to counteract the neuroadaptive changes caused by in vitro morphine treatment. The impact of Methadone, Cabergoline, and a combination of Cabergoline and Mdivi-1 on the cellular and molecular responses associated with Morphine-induced changes was studied in human Neuroblastoma (SK-N-MC) and Glioblastoma (U87-MG) cell lines that were exposed to prolong Morphine treatment. Cabergoline and Mdivi-1 combined treatment effectively influenced the molecular alterations associated with neuroadaptation in chronic morphine-exposed neural cells. This combination therapy normalized autophagy and reduced oxidative stress by enhancing total-antioxidant capacity, mitigating apoptosis, restoring BDNF expression, and balancing apoptotic elements. Our research outlines morphine's dual role in modulating mitochondrial dynamics via the dysregulation of the autophagy-apoptosis axis. This emphasizes the significant involvement of DRP1 activity in neurological adaptation processes, as well as disturbances in the dopaminergic pathway during in vitro chronic exposure to morphine in neural cells. This study proposes a novel approach by recommending the potential effectiveness of combining Cabergoline and Mdivi-1 to modulate the neuroadaptations caused by morphine. Additionally, we identified BDNF and PCNA in neural cells as potential neuroprotective markers for assessing the effectiveness of drugs against opioid toxicity, emphasizing the need for further validation. The study uncovers diverse effects observed in pretreated morphine glioblastoma cells under treatment with Cabergoline and methadone. This highlights the potential for new treatments in the DRD2 pathway and underscores the importance of investigating the interplay between autophagy and apoptosis to advance research in managing cancer-related pain. The study necessitates an in-depth investigation into the relationship between autophagy and apoptosis, with a specific emphasis on protein interactions and the dynamics of cell signaling.

Role of Autophagy-apoptosis Balance in Colorectal Cancer and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Colorectal cancer （CRC）， a malignant tumor of the digestive system， originates from the colorectal mucosa epithelium and is usually asymptomatic until it progresses to an advanced stage. With high incidence around the globe and the increasingly younger patients， this disease poses a serious threat to the health and lives of the patients. Although the pathogenesis of this disease is not fully understood， it is generally believed that it is associated with autophagy， apoptosis， and inflammation. Autophagy and apoptosis as two types of programmed cell death are subject to complex interactive regulation， and the imbalance between them is closely related to the occurrence， development， and prognosis of a variety of diseases. Studies have shown that autophagy-apoptosis balance plays a key role in CRC. On the one hand， autophagy and apoptosis coordinate with each other to inhibit CRC cell growth. On the other hand， autophagy can antagonize apoptosis to promote CRC cell growth. In clinical practice， surgery is often combined with radiotherapy and chemotherapy to treat CRC， which can control the progression of CRC to a certain extent but has serious adverse effects and poor long-term results. In recent years， traditional Chinese medicine （TCM） has been proved to be effective in the treatment of CRC. Studies have shown that numerous herbal active components can promote CRC cell death by regulating the autophagy-apoptosis balance， thereby blocking the progression of this disease. The process of autophagy-apoptosis balance in regulating cell activities has similar theoretical connotations with the Yin and Yang theory of TCM. Applying TCM in regulating autophagy-apoptosis balance at various stages of CRC has become a frontier， while the comprehensive elaboration remains to be conducted. By reviewing the relevant studies in recent years， this paper introduces the correlation between the Yin and Yang theory and the autophagy-apoptosis balance， the role of autophagy-apoptosis balance in CRC， and the research progress in the application of 27 Chinese herbal active components such as flavonoids， terpenoids， glycosides， and phenols capable of regulating autophagy-apoptosis balance in the treatment of CRC. The active components in Chinese medicines can recover the autophagy-apoptosis balance in CRC by acting on microtuble-associated protein 1 light chain 3（LC3）， Beclin-1， and B-cell lymphoma-2（Bcl-2）to regulate multiple signaling pathways such as protein kinase B（Akt）/mammalian target of rapamycin（mTOR）and reavtive oxygen species（ROS）/ c-Jun N-terminal kinase（JNK）， thus balancing Yin and Yang. This review aims to provide a reference for the treatment of CRC and the development of new drugs.